Microscopic (electron microscopy - including tracers, freeze-cleavage replication techniques; enzyme cytochemistry and immunocytochemistry at light and electron microscopy levels) and biochemical approaches will be used: (a) to study the structure of cytoplasmic organelles in order to gain a better understanding of organelle functions in normal, pathologic and maignant cells; and (b) to search for differences between malignant and normal cells in basic mechanisms of organelle-organelle and cell-cell interrelations. Dynamic interrelations of endoplasmic reticulum to the plasma membrane, Golgi apparatus, GERL, lysosomes and peroxisomes will be studied in a variety of cell types. These include hepatocytes and "littoral cells" (Kupffer cells, endothelial cells, lipocytes, etc.) in normal and altered rat livers: (a) in response to partial hepatectomy; (b) during the feeding of the hepatocarcinogen, 2-fluorenylacetamide (FAA); (c) in the "neoplastic nodules" induced by the FAA feeding regime of F.F. Becker; (d) adjacent to intraportally-injected islets isolated from rat pancreas; (e) in response to dietary regimes affecting hepatic transport and metabolism of lipid and lipoprotein; (f) during the uptake of ligands in which the terminal carbohydrate moieties are varied. The cell types will also include: 8a) cultured 3T3-L1 cells grown in different media; (b) tumor cells in the transplantable FAA-induced rat hepatomas (Becker), which produce normal plasma proteins and alpha-fetoprotein (alphaFP) and those which do not; and (c) cultured Morris 7777 hepatoma cells (these secrete high levels of alphaFP but essentially no albumin). We will continue attempts to isolate and characterize GERL from homogenates of normal and pathological rat liver. In neurons, our cytochemical studies will be extended to adenine arabinoside monophosphatate and other antiviral nucleic acid analogues. In 3T3-L1 cells we will attempt to isolate and characterize the acid phosphtase-positive coated vesicles which seem, from morphological appearances, to arise from GERL.